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Abstract BackgroundMobile apps represent accessible and cost-effective tools to improve nutrition and prevent chronic diseases. However, most of these apps have been characterized as having limited functionality, raising concerns about their effectiveness, acceptability, and efficacy. ObjectiveThe aims of the study were to assess the quality of popular nutrition-related app platforms in Spain and to describe their characteristics and functionalities. MethodsWe screened apps providing information on dietary advice, food advice, and nutritional content in the Apple App Store and Google Play Store in Spain from March 2 to March 16, 2024. Apps with a star rating of ≥4 (of 5 stars), those available in Spanish, those that were free of charge, those last updated after January 2022, those with >500 reviews, and those with >500,000 downloads were included. The quality of apps was assessed using the user version of the Mobile App Rating Scale (uMARS). General characteristics and nutritional, health, and market-related functionalities of the nutrition-related apps were described. Correlations among total and uMARS sections, star ratings, and number of reviews and downloads were evaluated. ResultsAmong the 1460 apps identified in the search, 42 apps met the criteria. The majority of these (n=20, 48%) aimed at recording and analyzing food intake, followed by those providing nutritional plans or diets (n=9, 21%), advising on healthy habits (n=7, 17%), and offering recipes (n=6, 14%). The most prevalent nutritional functionalities offered were recording and monitoring body measurements (n=30, 71%), food tracking (n=26, 62%), and dietary analysis (n=25, 60%), whereas nutrition education was less common (n=16, 38%). Among market-related functionalities, advertisements were the most common among the study apps (n=30, 71%), followed by the option of sharing on social media (n=29, 69%) and customizable reminders (n=26, 62%). Sharing the recorded information in the app with health professionals was infrequent (n=1, 2%). The mean (SD) total uMARS score (maximum 5 points) was 3.78 (0.35), while the mean (SD) uMARS scores for functionality, aesthetics, engagement, and information were 4.21 (0.38), 3.94 (0.54), 3.51 (0.46), and 3.48 (0.44), respectively. Lower mean scores were observed for the subjective quality (mean 2.65, SD 0.56) and perceived impact (mean 3.06, SD 0.67). Moderate to strong positive significant correlations were mostly observed between total uMARS and section-specific uMARS scores, while the correlations between the uMARS section scores were mostly moderate positive. Total uMARS scores were very weakly correlated with user rating, number of reviews, and number of downloads. ConclusionsThe quality of popular nutrition-related app platforms in Spain was acceptable, with observed remarkable differences between sections. The majority of the apps were appealing due to their user-friendly interfaces. Only a few apps, however, provided dietary structure analysis or nutritional education. Further research is needed to assess the long-term impact of these apps on users.

PM742 (1), a new chemical entity, has been isolated from the sponge Discodermia du Bocage collected in the Pacific Ocean. This compound showed strong in vitro cytotoxicity against several human tumor cell lines as well as a tubulin depolymerization mechanism of action, which led us to conduct an extensive Structure-Activity-Relationship study through the synthesis of different analogs. As a result, a derivatively named PM534 (2) is currently in its first human Phase I clinical trial. Herein, we present a comprehensive review of the isolation, structural elucidation, and antitumor activities of the parent compound PM742.

Lower back pain (LBP) describes pain of indeterminate duration between the lower edge of the ribs and the buttocks. LBP hinders movement, quality of life, and mental well-being, and limits work activities and engagement with family and friends. LBP represents a public health problem, and most workers are expected to experience LBP symptoms throughout their working lives. The study’s main objective was to characterize LBP in the hospitality population of the province of León, Spain, determining the risk factors. A pilot study with a cross-sectional observational design was developed following the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for 150 Spanish hotel workers. Sociodemographic and lifestyle, occupational, and clinical data related to LBP were obtained through surveys. The annual prevalence of LBP in this study was 87.1% which was higher in women. A significant relationship (p < 0.05) was obtained between sex, income, smoking, sleep quality, and all labor variables with LBP. In addition, the Fear Avoidance Beliefs Questionnaire (FABQ) results revealed that 49% of the participants had a score > 14. Also, 83.3% of patients with >6 annual LBP crises suffered from sciatica. Once the results were known, preventive intervention would be needed to reduce these main risk factors for LBP for hospitality workers.

Abstract Small‐Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC‐A and SCLC‐N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E‐box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles’s heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.

Low back pain (LBP) is a health problem that affects 70–80% of the population in Western countries. Because of the biomechanical relationship between the lumbar region and the hip, it is thought that strengthening the muscles of this joint could improve the symptoms of people with LBP. The objective of this study is to evaluate the current evidence on the efficacy of hip strengthening exercises to reduce pain and disability in people with LBP. Clinical trials were collected from the PubMed, PEDro, and Scopus databases published up to September 2022. Based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and using CASP and PEDro tools for methodological quality assessment, we selected studies that included hip strengthening exercises as part of LBP treatment and measured pain and/or disability parameters. Among the 966 records identified in the search, a total of 7 studies met the established selection criteria. Overall, participants who performed hip strengthening exercises had significantly improved in pain and disability. The methodological quality of the included studies was assessed as “good”. In conclusion, the addition of hip muscle strengthening exercises iterating interacted with LBP, effectively improving pain and disability.

Exercise capacity is limited by environmental heat stress because thermoregulatory systems are altered and cannot prevent the elevation of body temperature due to a complex interplay of physiological, physical, and perceptual alterations. Cooling is an effective strategy to attenuate the temperature rise. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PEDro scale for assessing methodological quality, we systematically reviewed studies indexed in Medline, Web of Science, EMBASE, Science Direct, Sportdiscus, and Scopus, to evaluate the effects of the cooling vest (CVs) on perceptual response, physiological behavior, and sports performance in adult physical activity practitioners under heat stress conditions. Among the 711 studies identified in the search, 10 studies for the systematic review and eight for the meta-analysis met the inclusion and exclusion criteria. Overall, the use of CVs showed improvements in certain sports performance indicators, being significant (p < 0.05) in test time and substantial in peak power that could be influenced directly by the significant reduction (p < 0.05) in skin temperature and indirectly by the significant improvement (p < 0.05) in thermal and exertional perceptual responses, without the involvement of core temperature. In conclusion, the use of CVs is a cooling technique that influences perceptual response, thermo-physiological behavior, and sports performance. However, further studies are needed to elucidate the relevance of its application to CVs.

In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no specific and effective treatment for their management. Currently, therapeutic exercise strategies (ThEx) are effective in many diseases by reducing the appearance of complications and side effects linked to treatment, and are consequently of great relevance. In this study, we review the effect of ThEX in reversing decreased strength, impaired respiratory function, decreased physical fitness, and decreased quality of life (QoL) caused by post-COVID-19 syndrome. A literature search was conducted through the electronic databases, Medline (PubMed), SciELO and Cochrane Library Plus for this structured narrative review for studies published from database retrieval up till 12 December 2022. A total of 433 patients with post-COVID-19 syndrome condition (60% women) were included in the nine studies which met the inclusion/exclusion criteria. Overall, post-COVID-19 syndrome patients who followed a ThEx intervention showed improvements in strength, respiratory function, physical fitness and QoL, with no exercise-derived side effects. Thus, ThEx based on strength, aerobic and respiratory training could be an adjuvant non-pharmacological tool in the modulation of post-COVID-19 syndrome.

Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of beta-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (DeltaPsim) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of beta-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 3'UTR of the transcript. The 3'UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated beta-F1-ATPase expression in human cancer.

Abstract The plasticity of cancer cells facilitates their ability to adopt heterogeneous differentiation states, posing a significant challenge to therapeutic interventions. Specific gene expression programs, driven in part by super-enhancers (SEs), underlie cancer cell states. Here we successfully inhibit SE-driven transcription in phenotypically distinct metastatic melanoma cells using next-generation synthetic ecteinascidins. Through functional genomic methodologies, we demonstrate that these compounds inhibit the expression of genes encoding lineage-specific or ubiquitous transcription factors/coactivators by selectively targeting the CpG-rich sequences within their promoters and/or enhancers. This prevents the formation of transcription factor/coactivator condensates necessary for SE-dependent gene expression. Consequently, these compounds exhibit cytotoxic activity across distinct subpopulations of metastatic melanoma cells and inhibit tumor proliferation, including those resistant to current therapies. These findings extend to other cancers, like small cell lung cancer, recently approved for ecteinascidin-based treatment. Overall, our study provides preclinical proof that pan-inhibition of SE-dependent genes with synthetic ecteinascidins is a promising therapeutic approach for tumors with heterogeneous transcriptional landscapes.

There is a large body of clinical data documenting that most human carcinomas contain reduced levels of the catalytic subunit of the mitochondrial H+-ATP synthase. In colon and lung cancer this alteration correlates with a poor patient prognosis. Furthermore, recent findings in colon cancer cells indicate that downregulation of the H+-ATP synthase is linked to the resistance of the cells to chemotherapy. However, the mechanism by which the H+-ATP synthase participates in cancer progression is unknown. In this work, we show that inhibitors of the H+-ATP synthase delay staurosporine (STS)-induced cell death in liver cells that are dependent on oxidative phosphorylation for energy provision whereas it has no effect on glycolytic cells. Efficient execution of cell death requires the generation of reactive oxygen species (ROS) controlled by the activity of the H+-ATP synthase in a process that is concurrent with the rapid disorganization of the cellular mitochondrial network. The generation of ROS after STS treatment is highly dependent on the mitochondrial membrane potential and most likely caused by reverse electron flow to Complex I. The generated ROS promote the carbonylation and covalent modification of cellular and mitochondrial proteins. Inhibition of the activity of the H+-ATP synthase blunted ROS production prevented the oxidation of cellular proteins and the modification of mitochondrial proteins delaying the release of cytochrome c and the execution of cell death. The results in this work establish the downregulation of the H+-ATP synthase, and thus of oxidative phosphorylation, as part of the molecular strategy adapted by cancer cells to avoid ROS-mediated cell death. Furthermore, the results provide a mechanistic explanation to understand chemotherapeutic resistance of cancer cells that rely on glycolysis as the main energy provision pathway. [ABSTRACT FROM AUTHOR]

Purpose: Trabectedin induces synthetic lethality in tumor cells carrying defects in homologous recombinant DNA repair. We evaluated the effect of concomitant inhibition of nucleotide-excision repair and poly (ADP-ribose) polymerase (PARP) activity with trabectedin and PARP inhibitors, respectively, and whether the synthetic lethality effect had the potential for a synergistic effect in breast cancer cell lines. Additionally, we investigated if this approach remained effective in BRCA1-positive breast tumor cells., Methods: We have evaluated the in vitro synergistic effect of combinations of trabectedin and three different PARP inhibitors (veliparib, olaparib, and iniparib) in four breast cancer cell lines, each presenting a different BRCA1 genetic background. Antiproliferative activity, DNA damage, cell cycle perturbations and poly(ADP-ribosyl)ation were assessed by MTT assay, comet assay, flow cytometry and western blot, respectively., Results: The combination of trabectedin and olaparib was synergistic in all the breast cancer cell lines tested. Our data indicated that the synergy persisted regardless of the BRCA1 status of the tumor cells. Combination treatment was associated with a strong accumulation of double-stranded DNA breaks, G2/M arrest, and apoptotic cell death. Synergistic effects were not observed when trabectedin was combined with veliparib or iniparib., Conclusion: Collectively, our results indicate that the combination of trabectedin and olaparib induces an artificial synthetic lethality effect that can be used to kill breast cancer cells, independent of BRCA1 status.